New molecular bridge between RelA/p65 and NF-κB target genes via histone acetyltransferase TIP60 cofactor.

The nuclear factor-κB (NF-κB) family is involved in the expressions of numerous genes, in development, apoptosis, inflammatory responses, and oncogenesis. In this study we identified four NF-κB target genes that are modulated by TIP60. We also found that TIP60 interacts with the NF-κB RelA/p65 subunit and increases its transcriptional activity ...
through protein-protein interaction. Although TIP60 binds with RelA/p65 using its histone acetyltransferase domain, TIP60 does not directly acetylate RelA/p65. However, TIP60 maintained acetylated Lys-310 RelA/p65 levels in the TNF-α-dependent NF-κB signaling pathway. In chromatin immunoprecipitation assay, TIP60 was primarily recruited to the IL-6, IL-8, C-IAP1, and XIAP promoters in TNF-α stimulation followed by acetylation of histones H3 and H4. Chromatin remodeling by TIP60 involved the sequential recruitment of acetyl-Lys-310 RelA/p65 to its target gene promoters. Furthermore, we showed that up-regulated TIP60 expression was correlated with acetyl-Lys-310 RelA/p65 expressions in hepatocarcinoma tissues. Taken together these results suggest that TIP60 is involved in the NF-κB pathway through protein interaction with RelA/p65 and that it modulates the transcriptional activity of RelA/p65 in NF-κB-dependent gene expression.
Mesh Terms:
Acetylation, Carcinoma, Hepatocellular, Gene Expression Regulation, Neoplastic, HEK293 Cells, Hep G2 Cells, Histone Acetyltransferases, Histones, Humans, Inhibitor of Apoptosis Proteins, Interleukin-6, Interleukin-8, Liver Neoplasms, Neoplasm Proteins, Promoter Regions, Genetic, Transcription Factor RelA, Tumor Necrosis Factor-alpha, Up-Regulation, X-Linked Inhibitor of Apoptosis Protein
J. Biol. Chem.
Date: Mar. 02, 2012
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